The primary objective of the proposed research is to gather basic information on the mechanisms by which alterations in energy metabolism influence feeding behavior. The research plan is designed to achieve two interrelated goals: 1) to characterize the metabolic events underlying alterations in food intake that occur in response to experimental manipulations of fuel homeostasis, and 2) to identify the role of the liver in this metabolic control of food intake. Metabolic parameters will be measured under controlled feeding conditions in order to prevent compensatory changes in food intake from confounding the metabolic variables under study. These measures are intended to provide a profile of metabolic fuels in the circulation and in reserves, as well as to provide several indicies of the state of hepatic energy metabolism. Experiments are described in which quantitative relationships between dietary energy content, food intake, and various metabolic parameters will be examined in normal rats and rats with experimental diabetes mellitus. Other studies will examine the effects of insulin and 2-deoxyglucose treatment on food intake and metabolism in order to determine to what extent alterations in peripheral metabolism underlie the effects of these treatments on food intake. Finally, the effects of selective denervation of the liver will be studied in order to determine whether the liver is involved in the control of food intake under normal conditions and during experimental manipulations of energy metabolism.